Pazopanib Hydrochloride In Treating Patients With Advanced Neuroendocrine Cancer

Study Overview

Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

This phase II trial studies how well pazopanib hydrochloride works in treating patients with advanced neuroendocrine cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) (complete and partial response) of GW786034 (pazopanib hydrochloride) 800 mg administered orally once daily in patients with advanced low or intermediate grade carcinoid tumors (in carcinoid cohort). II. To determine the objective response rate (ORR) (complete response and partial response) of GW786034 800mg administered orally once daily in patients with advanced low or intermediate grade pancreatic islet cell carcinoma (in islet cell cohort). SECONDARY OBJECTIVES: I. To determine the progression free survival (PFS) duration of GW786034 800mg administered orally once daily in patients with low grade neuroendocrine carcinoma. II. To determine the safety and tolerability of GW786034 800mg administered orally once daily in patients with low grade neuroendocrine carcinoma. III. To explore the effect on tumor blood flow as determined by functional computed tomography (CT) of GW786034 800 mg orally once daily in patients with low grade neuroendocrine carcinoma. IV. To assess the trough level of GW786034 800 mg orally once daily in patients with low grade neuroendocrine carcinoma. OUTLINE: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 90 days for up to 18 months.

Gastrin-Producing Neuroendocrine Tumor
Lung Carcinoid Tumor
Metastatic Digestive System Neuroendocrine Tumor G1
Multiple Endocrine Neoplasia Type 1
Pancreatic Glucagonoma
Pancreatic Insulinoma
Pancreatic Polypeptide Tumor
Recurrent Digestive System Neuroendocrine Tumor G1
Recurrent Pancreatic Neuroendocrine Carcinoma
Regional Digestive System Neuroendocrine Tumor G1
Somatostatin-Producing Neuroendocrine Tumor

OTHER: Laboratory Biomarker Analysis
DRUG: Pazopanib Hydrochloride
OTHER: Pharmacological Study

NCI-2009-00201
NCI-2009-00201 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CDR0000537034
MDACC 2006-0077
MDACC 2006-0077 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)
7650 (OTHER Identifier) (OTHER: CTEP)
N01CM62202 (U.S. NIH Grant/Contract)
P30CA016672 (U.S. NIH Grant/Contract)
U01CA062490 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-03-27	Results First Submitted 2015-01-22	Last Update Submitted that met QC Criteria 2020-03-25
First Submitted that Met QC Criteria 2007-03-27	Results First Submitted that Met QC Criteria 2015-03-18	Last Update Posted (ACTUAL) 2020-04-03
First Posted (ACTUAL) 2007-03-30	Results First Posted 2015-04-01	Last Verified 2020-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (pazopanib hydrochloride) Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	OTHER: Laboratory Biomarker Analysis Correlative studies DRUG: Pazopanib Hydrochloride Given PO OTHER: Pharmacological Study Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (pazopanib hydrochloride)

Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

OTHER: Laboratory Biomarker Analysis

Correlative studies

DRUG: Pazopanib Hydrochloride

Given PO

OTHER: Pharmacological Study

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (Complete and Partial Response) for Each Cohort Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)	RECIST Criteria: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance 1/> new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.	Up to 18 months

Secondary Outcome Measures	Measure Description	Time Frame
Percent Change in Tumor Blood Flow Assessed by Functional CT	Explore the effect on tumor blood flow as determined by functional CT of GW786034 (Pazopanib) 800 mg orally once daily on both arms, carcinoid and pNET.	Baseline and week 12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
21 Years

Accepts Healthy Volunteers:

Patients must have histologically or cytologically confirmed low or intermediate grade carcinoid or islet cell carcinoma; patients with carcinoid or islet cell carcinoma associated with multiple endocrine neoplasia (MEN)1 syndrome will be eligible and entered in the islet cell cohort
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
Patients may have received 0 or 1 prior cytotoxic therapy; chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen; patient must not have received prior bevacizumab or any other therapy targeting vascular endothelial growth factor (VEGF) or VEGF receptors (i.e., SU11248, PTK787/ZK222584, Sorafenib, GW786034)
Patients must be on a stable dose of somatostatin analogue for 2 months prior to start of protocol; octreotide dose not count toward prior therapy
Prior radiation therapy is permitted; a recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment
Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy)
Patients may have received prior therapy targeting v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (c-kit), c-abl oncogene 1, non-receptor tyrosine kinase (abl), platelet-derived growth factor receptor (PDGFR), or epidermal growth factor receptor (EGFR) (imatinib, gefitinib, erlotinib, cetuximab; not counted toward prior cytotoxic chemotherapy)
Patients must have unresectable or metastatic disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1 (Karnofsky >= 70%)
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 120,000/mcL
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
Creatinine =< 2.0 OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (calculated by Cockcroft Gault formula)
Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 1.2 X the upper limit of normal
Patients must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation; women of child-bearing potential must have a negative blood pregnancy test prior to study entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

An intrauterine device with a documented failure rate of less than 1% per year
Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female
Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 21 days after the last dose of investigational product
Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide)

Note: Oral contraceptives are not reliable due to potential drug-drug interaction
Ability to understand and the willingness to sign a written informed consent document
Ability to swallow and retain oral medication

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to study enrollment; at least 4 weeks must have elapsed since any major surgery prior to study enrollment
Patients may not be receiving any other investigational agents
Patients with corrected QT (QTc) > 480 msecs
Patients with greater than 1+ (>= 100 mg/dl) proteinuria on two consecutive routine urinalysis taken at least 1 week apart are ineligible
Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro data indicate that the agent has the potential to interact with the cytochrome P450 isoenzymes; certain other agents should be used with caution
Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GW786034 (pazopanib) tablets are excluded
Patients with any of the following conditions are excluded:

Serious or non-healing wound, ulcer, or bone fracture
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
History of known active diverticulitis within the past 3 months
Any history of cerebrovascular accident (CVA) within the last 6 months
Current use of therapeutic warfarin; Note: Low molecular weight heparin and prophylactic low-dose warfarin are permitted; PT/PTT must meet the inclusion criteria
History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks
History of venous thrombosis in last 12 weeks
Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
Patients with known brain metastases should be excluded from this clinical trial
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GW786034 (pazopanib); these potential risks may also apply to other agents used in this study
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Uncontrolled diarrhea (8 or more bowel movements per day)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: James Yao, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Phan AT, Halperin DM, Chan JA, Fogelman DR, Hess KR, Malinowski P, Regan E, Ng CS, Yao JC, Kulke MH. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol. 2015 Jun;16(6):695-703. doi: 10.1016/S1470-2045(15)70136-1. Epub 2015 May 5.

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Clinical Trial Record